tbuckley/cabot-search huggingface dataset:
The EAT–Lancet reference diet and cognitive function across the life course
Authors: Boushra Dalile, Curie Kim, Andy Challinor, Lucie Geurts, Eileen R Gibney, Marcelo V Galdos, Giorgio La Fata, Sophie Layé, John C Mathers, David Vauzour, J Martin Verkuyl, Sandrine Thuret
Journal: The Lancet Planetary Health (2022)

The EAT–Lancet Commission devised a sustainable reference diet with the aim of reducing the incidence of non-communicable diseases and mortality globally while improving food system sustainability. The extent to which the reference diet supports cognitive function across the life course, however, has not yet been evaluated. This Review assesses the evidence for diet supporting cognitive function from childhood into old age. A comprehensive but non-exhaustive literature search was done, synthesising studies that investigated the effect of whole foods on cognition in healthy, community-dwelling human participants. We found that the current evidence base is weak with mixed conclusions and multiple methodological caveats, which precludes strong conclusions pertaining to the suitability of dietary recommendations for each food group per age group. Long-term intervention and prospective cohort studies are needed to reduce this knowledge deficit. Revising dietary recommendations with the aim of maintaining an adequate nutrient intake to sustain healthy cognitive function across the life course could be worthwhile. This Review outlines recommendations for future work to help improve the current knowledge deficit regarding dietary intake and cognitive function across the life course and its implications for dietary guidelines such as the EAT–Lancet Commission.
HIV, Subclinical Cardiovascular Disease, and Clinical Progression
Authors: Matthew J. Feinstein
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Unveiling the tumor immune microenvironment of organ-specific melanoma metastatic sites
Authors: Jordan W Conway, Robert V Rawson, Serigne Lo, Tasnia Ahmed, Ismael A Vergara, Tuba N Gide, Grace Heloise Attrill, Matteo S Carlino, Robyn P M Saw, John F Thompson, Andrew J Spillane, Kerwin F Shannon, Brindha Shivalingam, Alexander Maxwell Menzies, James S Wilmott, Georgina V Long, Richard A Scolyer, Ines Pires da Silva
Journal: Journal for ImmunoTherapy of Cancer (2022)

The liver is a known site of resistance to immunotherapy and the presence of liver metastases is associated with shorter progression-free and overall survival (OS) in melanoma, while lung metastases have been associated with a more favorable outcome. There are limited data available regarding the immune microenvironment at different anatomical sites of melanoma metastases. This study sought to characterize and compare the tumor immune microenvironment of liver, brain, lung, subcutaneous (subcut) as well as lymph node (LN) melanoma metastases.We analyzed OS in 1924 systemic treatment-naïve patients with AJCC (American Joint Committee on Cancer) stage IV melanoma with a solitary site of organ metastasis. In an independent cohort we analyzed and compared immune cell densities, subpopulations and spatial distribution in tissue from liver, lung, brain, LN or subcut sites from 130 patients with stage IV melanoma.Patients with only liver, brain or bone metastases had shorter OS compared to those with lung, LN or subcutaneous and soft tissue metastases. Liver and brain metastases had significantly lower T-cell infiltration than lung (p=0.0116 and p=0.0252, respectively) and LN metastases (p=0.0116 and p=0.0252, respectively). T cells were further away from melanoma cells in liver than lung metastases (p=0.0335). Liver metastases displayed unique T-cell profiles, with a significantly lower proportion of programmed cell death protein-1+ T cells compared to all other anatomical sites (p<0.05), and a higher proportion of TIM-3+ T cells compared to LN (p=0.0004), subcut (p=0.0082) and brain (p=0.0128) metastases. Brain metastases had a lower macrophage density than subcut (p=0.0105), liver (p=0.0095) and lung (p<0.0001) metastases. Lung metastases had the highest proportion of programmed death ligand-1+ macrophages of the total macrophage population, significantly higher than brain (p<0.0001) and liver metastases (p=0.0392).Liver and brain melanoma metastases have a significantly reduced immune infiltrate than lung, subcut and LN metastases, which may account for poorer prognosis and reduced immunotherapy response rates in patients with liver or brain metastases. Increased TIM-3 expression in liver metastases suggests TIM-3 inhibitor therapy as a potential therapeutic opportunity to improve patient outcomes.
Effects of Empagliflozin in Women and Men With Heart Failure and Preserved Ejection Fraction
Authors: Javed Butler, Gerasimos Filippatos, Tariq Jamal Siddiqi, João Pedro Ferreira, Martina Brueckmann, Edimar Bocchi, Michael Böhm, Vijay K. Chopra, Nadia Giannetti, Tomoko Iwata, James L. Januzzi, Sanjay Kaul, Ileana L. Piña, Piotr Ponikowski, Ursula Rauch-Kröhnert, Sanjiv J. Shah, Michele Senni, Mikhail Sumin, Subodh Verma, Jian Zhang, Stuart J. Pocock, Faiez Zannad, Milton Packer, Stefan D. Anker
Journal: Circulation (2022)

Women and men with heart failure (HF) and preserved ejection fraction may differ in their clinical characteristics and their response to therapy. The aim of this study was to evaluate the influence of sex on the effects of empagliflozin in patients with HF and preserved ejection fraction enrolled in the EMPEROR-Preserved trial (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Preserved Ejection Fraction).The effects of empagliflozin on the primary outcome of cardiovascular death or hospitalization for HF and on secondary outcomes (including total HF hospitalization, cardiovascular and all-cause mortality, and Kansas City Cardiomyopathy Questionnaire scores) were compared in women and men in the overall cohort and in subgroups defined by left ventricular ejection fraction (41%-49%, 50%-59%, and ≥60%). The effects of empagliflozin on physiological measures, including changes in systolic blood pressure, uric acid, hemoglobin, body weight, and natriuretic peptide levels, were also assessed.Of the 5988 patients randomized, 2676 (44.7%) were women. In the placebo arm, women tended to have lower risk for adverse outcomes, including a lower risk of all-cause mortality (hazard ratio, 0.69 [95% CI, 0.56, 0.84]). Compared with placebo, empagliflozin reduced the risk of cardiovascular death or hospitalization for HF to a similar degree in both sexes (hazard ratio, 0.81 [95% CI, 0.69, 0.96] for men; and hazard ratio, 0.75 [95% CI, 0.61, 0.92] for women; Pinteraction=0.54). Sex did not modify the relationship between empagliflozin and outcomes across ejection fraction groups. Similar results were seen for secondary outcomes and physiological measures. Compared with placebo, empagliflozin improved the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score to a similar extent in both sexes (1.38 for men versus 1.63 for women at 52 weeks; Pinteraction=0.77); the results were similar for Kansas City Cardiomyopathy Questionnaire overall summary score and total summary score.Empagliflozin produced similar benefits on outcomes and health status in women and men with HF and preserved ejection fraction.URL: https://www.gov; Unique identifier: NCT03057951.
Development and Validation of the Summary Elixhauser Comorbidity Score for Use With ICD-10-CM–Coded Data Among Older Adults
Authors: Hemalkumar B. Mehta, Shuang Li, Huijun An, James S. Goodwin, G. Caleb Alexander, Jodi B. Segal
Journal: Annals of Internal Medicine (2022)

Background: Older adults have many comorbidities contributing to mortality. Objective: To develop a summary Elixhauser (S-Elixhauser) comorbidity score to predict 30-day, in-hospital, and 1-year mortality in older adults using the 38 comorbidities operationalized by the Agency for Healthcare Research and Quality (AHRQ). Design: Retrospective cohort study. Setting: Medicare beneficiaries from 2017 to 2019. Patients: Persons hospitalized in 2018 (n = 899 844) and 3 disease-specific hospitalized cohorts. Measurements: Weights were derived for 38 comorbidities to predict 30-day, in-hospital, and 1-year mortality. The S-Elixhauser score was internally validated and calibrated. Individual Elixhauser comorbidity indicators (38 comorbidities), the modified application of the AHRQ-derived Elixhauser summary score, the Charlson comorbidity indicators (17 comorbidities), and the Charlson summary score were externally validated. The c-statistic was used to evaluate discrimination of a comorbidity score model. Results: The S-Elixhauser score was well calibrated and internally validated, with a c-statistic of 0.705 (95% CI, 0.703 to 0.707) in predicting 30-day mortality, 0.654 (CI, 0.651 to 0.657) for in-hospital mortality, and 0.743 (CI, 0.741 to 0.744) for 1-year mortality. In external validation of other comorbidity indices for 30-day mortality, the c-statistic was 0.711 (CI, 0.709 to 0.713) for the individual Elixhauser comorbidity indicators, 0.688 (CI, 0.686 to 0.690) for the AHRQ Elixhauser score, 0.696 (CI, 0.694 to 0.698) for the Charlson comorbidity indicators, and 0.690 (CI, 0.688 to 0.693) for the Charlson summary score. In 3 disease-specific populations, the discrimination of the S-Elixhauser score in predicting 30-day mortality ranged from 0.657 to 0.732. Limitation: Validation of the S-Elixhauser comorbidity score and head-to-head comparison with other comorbidity scores in an external population are needed to evaluate comparative performance. Conclusion: The S-Elixhauser comorbidity score is well calibrated and internally validated but its advantage over the AHRQ Elixhauser and Charlson summary scores is unclear. Primary Funding Source: National Institute on Aging.
Induction of natural IgE by glucocorticoids
Authors: Jaechul Lim, Erica V. Lin, Jun Young Hong, Bharat Vaidyanathan, Steven A. Erickson, Charles Annicelli, Ruslan Medzhitov
Journal: The Journal of Experimental Medicine (2022)

IgE mediates allergic responses by coating mast cell or basophil surfaces and inducing degranulation upon binding a specific allergen. IgE can also be spontaneously produced in the absence of foreign allergens; yet the origin, regulation, and functions of such “natural” IgE still remain largely unknown. Here, we find that glucocorticoids enhance the production of IgE in B cells both in vivo and ex vivo without antigenic challenge. Such IgE production is promoted by B cell–intrinsic glucocorticoid receptor signaling that reinforces CD40 signaling and synergizes with the IL-4/STAT6 pathway. In addition, we found that rare B cells in the mesenteric lymph nodes are responsible for the production of glucocorticoid-inducible IgE. Furthermore, locally produced glucocorticoids in the gut may induce natural IgE during perturbations of gut homeostasis, such as dysbiosis. Notably, mice preemptively treated with glucocorticoids were protected from subsequent pathogenic anaphylaxis. Together, our results suggest that glucocorticoids, classically considered to be broadly immunosuppressive, have a selective immunostimulatory role in B cells.
Risk factors for severe infection and mortality in COVID-19 and monoclonal gammopathy of undetermined significance
Authors: Matthew Ho, Saurabh Zanwar, Francis K. Buadi, Sikander Ailawadhi, Jeremy Larsen, Leif Bergsagel, Moritz Binder, Asher Chanan-Khan, David Dingli, Angela Dispenzieri, Rafael Fonseca, Morie A. Gertz, Wilson Gonsalves, Ronald S. Go, Suzanne Hayman, Prashant Kapoor, Taxiarchis Kourelis, Martha Q. Lacy, Nelson Leung, Yi Lin, Eli Muchtar, Vivek Roy, Taimur Sher, Rahma Warsame, Amie Fonder, Miriam Hobbs, Yi L. Hwa, Robert A. Kyle, S. Vincent Rajkumar, Shaji Kumar
Journal: Blood (2022)
Quantitative Micro-Elastography Enables <i>In Vivo</i> Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery
Authors: Peijun Gong, Synn Lynn Chin, Wes M. Allen, Helen Ballal, James D. Anstie, Lixin Chin, Hina M. Ismail, Renate Zilkens, Devina D. Lakhiani, Matthew McCarthy, Qi Fang, Daniel Firth, Kyle Newman, Caleb Thomas, Jiayue Li, Rowan W. Sanderson, Ken Y. Foo, Chris Yeomans, Benjamin F. Dessauvagie, Bruce Latham, Christobel M. Saunders, Brendan F. Kennedy
Journal: Cancer Research (2022)

Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery. However, current QME methods, in common with most proposed intraoperative solutions, cannot image cancer directly in the patient, making their translation to clinical use challenging. In this proof-of-concept study, we aimed to determine whether a handheld QME probe, designed to interrogate the surgical cavity, can detect residual cancer directly in the breast cavity in vivo during BCS. In a first-in-human study, 21 BCS patients were scanned in vivo with the QME probe by five surgeons. For validation, protocols were developed to coregister in vivo QME with postoperative histopathology of the resected tissue to assess the capability of QME to identify residual cancer. In four cavity aspects presenting cancer and 21 cavity aspects presenting benign tissue, QME detected elevated stiffness in all four cancer cases, in contrast to low stiffness observed in 19 of the 21 benign cases. The results indicate that in vivo QME can identify residual cancer by directly imaging the surgical cavity, potentially providing a reliable intraoperative solution that can enable more complete cancer excision during BCS.Optical imaging of microscale tissue stiffness enables the detection of residual breast cancer directly in the surgical cavity during breast-conserving surgery, which could potentially contribute to more complete cancer excision.
Ecosystem restoration is integral to humanity's recovery from COVID-19
Authors: Jake M Robinson, James Aronson, Christopher B Daniels, Neva Goodwin, Craig Liddicoat, Laura Orlando, David Phillips, Jessica Stanhope, Philip Weinstein, Adam T Cross, Martin F Breed
Journal: The Lancet Planetary Health (2022)

COVID-19 has devastated global communities and economies. The pandemic has exposed socioeconomic disparities and weaknesses in health systems worldwide. Long-term health effects and economic recovery are major concerns. Ecosystem restoration-ie, the repair of ecosystems that have been degraded-relates directly to tackling the health and socioeconomic burdens of COVID-19, because stable and resilient ecosystems are fundamental determinants of health and socioeconomic stability. Here, we use COVID-19 as a case study, showing how ecosystem restoration can reduce the risk of infection and adverse sequelae and have an integral role in humanity's recovery from COVID-19. The next decade will be crucial for humanity's recovery from COVID-19 and for ecosystem repair. Indeed, in the absence of effective, large-scale restoration, 95% of the Earth's land could be degraded by 2050. The UN Decade on Ecosystem Restoration (2021-30) declaration reflects the growing urgency and scale at which we should repair ecosystems. Importantly, ecosystem restoration could also help to combat the health and socioeconomic issues that are associated with COVID-19, yet it is poorly integrated into current responses to the disease. Ecosystem restoration can be a core public health intervention and assist in COVID-19 recovery if it is closely integrated with socioeconomic, health, and environmental policies.
Transit-amplifying cells control R-spondins in the mouse crypt to modulate intestinal stem cell proliferation
Authors: Almudena Chaves-Pérez, Karla Santos-de-Frutos, Sergio de la Rosa, Irene Herranz-Montoya, Cristian Perna, Nabil Djouder
Journal: The Journal of Experimental Medicine (2022)

Intestinal epithelium regenerates rapidly through proliferation of intestinal stem cells (ISCs), orchestrated by potent mitogens secreted within the crypt niche. However, mechanisms regulating these mitogenic factors remain largely unknown. Here, we demonstrate that transit-amplifying (TA) cells, marked by unconventional prefoldin RPB5 interactor (URI), control R-spondin production to guide ISC proliferation. Genetic intestinal URI ablation in mice injures TA cells, reducing their survival capacity, leading to an inflamed tissue and subsequently decreasing R-spondin levels, thereby causing ISC quiescence and disruption of intestinal structure. R-spondin supplementation or restoration of R-spondin levels via cell death inhibition by c-MYC elimination or the suppression of inflammation reinstates ISC proliferation in URI-depleted mice. However, selective c-MYC and p53 suppression are required to fully restore TA cell survival and differentiation capacity and preserve complete intestinal architecture. Our data reveal an unexpected role of TA cells, which represent a signaling platform instrumental for controlling inflammatory cues and R-spondin production, essential for maintaining ISC proliferation and tissue regeneration.
The Single-Cell Immunogenomic Landscape of B and Plasma Cells in Early-Stage Lung Adenocarcinoma
Authors: Dapeng Hao, Guangchun Han, Ansam Sinjab, Lorena Isabel Gomez-Bolanos, Rossana Lazcano, Alejandra Serrano, Sharia D. Hernandez, Enyu Dai, Xuanye Cao, Jian Hu, Minghao Dang, Ruiping Wang, Yanshuo Chu, Xingzhi Song, Jianhua Zhang, Edwin R. Parra, Jennifer A. Wargo, Stephen G. Swisher, Tina Cascone, Boris Sepesi, Andrew P. Futreal, Mingyao Li, Steven M. Dubinett, Junya Fujimoto, Luisa M. Solis Soto, Ignacio I. Wistuba, Christopher S. Stevenson, Avrum Spira, Shabnam Shalapour, Humam Kadara, Linghua Wang
Journal: Cancer Discovery (2022)

Abstract Tumor-infiltrating B and plasma cells (TIB) are prevalent in lung adenocarcinoma (LUAD); however, they are poorly characterized. We performed paired single-cell RNA and B-cell receptor (BCR) sequencing of 16 early-stage LUADs and 47 matching multiregion normal tissues. By integrative analysis of ∼50,000 TIBs, we define 12 TIB subsets in the LUAD and adjacent normal ecosystems and demonstrate extensive remodeling of TIBs in LUADs. Memory B cells and plasma cells (PC) were highly enriched in tumor tissues with more differentiated states and increased frequencies of somatic hypermutation. Smokers exhibited markedly elevated PCs and PCs with distinct differentiation trajectories. BCR clonotype diversity increased but clonality decreased in LUADs, smokers, and with increasing pathologic stage. TIBs were mostly localized within CXCL13+ lymphoid aggregates, and immune cell sources of CXCL13 production evolved with LUAD progression and included elevated fractions of CD4 regulatory T cells. This study provides a spatial landscape of TIBs in early-stage LUAD. Significance: While TIBs are highly enriched in LUADs, they are poorly characterized. This study provides a much-needed understanding of the transcriptional, clonotypic states and phenotypes of TIBs, unraveling their potential roles in the immunopathology of early-stage LUADs and constituting a road map for the development of TIB-targeted immunotherapies for the treatment of this morbid malignancy. This article is highlighted in the In This Issue feature, p. 2483
Incidence of subsequent malignancies after total body irradiation-based allogeneic HSCT in children with ALL – long-term follow-up from the prospective ALL-SCT 2003 trial
Authors: Anna Eichinger, Ulrike Poetschger, Evgenia Glogova, Peter Bader, Oliver Basu, Rita Beier, Birgit Burkhardt, Carl-Friedrich Classen, Alexander Claviez, Selim Corbacioglu, Hedwig E. Deubzer, Johann Greil, Bernd Gruhn, Tayfun Güngör, Kinan Kafa, Jörn-Sven Kühl, Peter Lang, Bjoern Soenke Lange, Roland Meisel, Ingo Müller, Martin G. Sauer, Paul-Gerhardt Schlegel, Ansgar Schulz, Daniel Stachel, Brigitte Strahm, Angela Wawer, Christina Peters, Michael H. Albert
Journal: Leukemia (2022)

Abstract Total body irradiation (TBI)-based conditioning is associated with superior leukemia-free survival in children with ALL undergoing HSCT. However, the risk for subsequent malignant neoplasms (SMN) remains a significant concern. We analyzed 705 pediatric patients enrolled in the prospective ALL-SCT-BFM-2003 trial and its subsequent registry. Patients &gt;2 years received conditioning with TBI 12 Gy/etoposide ( n = 558) and children ≤2 years of age or with contraindications for TBI received busulfan/cyclophosphamide/etoposide ( n = 110). The 5- and 10-year cumulative incidence of SMN was 0.02 ± 0.01 and 0.13 ± 0.03, respectively. In total, 39 SMN (34 solid tumors, 5 MDS/AML) were diagnosed in 33 patients at a median of 5.8 years (1.7–13.4), exclusively in the TBI group. Of 33 affected patients, 21 (64%) are alive at a median follow-up of 5.1 years (0–9.9) after diagnosis of their first SMN. In univariate analysis, neither age at HSCT, donor type, acute GVHD, chronic GVHD, nor CMV constituted a significant risk factor for SMN. The only significant risk factor was TBI versus non-TBI based conditioning. This analysis confirms and quantifies the increased risk of SMN in children with ALL after conditioning with TBI. Future strategies to avoid TBI will need careful tailoring within prospective, controlled studies to prevent unfavorable outcomes.